Cardiac inflammation and diastolic dysfunction in hypercholesterolemic rabbits.

Area of Science:

• Cardiovascular Research
• Animal Models of Disease
• Heart Failure Pathophysiology

Background:

• Left ventricular diastolic dysfunction (LVDD) affects over 50% of heart failure patients.
• Existing LVDD animal models are limited, hindering mechanistic understanding.
• Aortic valve stenosis (AVS) can cause LVDD, but models without AVS are needed.

Purpose of the Study:

• To develop a novel rabbit model of LVDD independent of AVS.
• To investigate the cardiac effects of a hypercholesterolemic diet in rabbits.

Main Methods:

• Rabbits were fed cholesterol-enriched or normal diets.
• Echocardiography assessed cardiac structure and function over 20 weeks.
• Histological and gene expression analyses (RT-qPCR) were performed on left ventricular samples.

Main Results:

• A hypercholesterolemic diet induced LVDD, evidenced by echocardiographic parameters (e.g., E/Em ratio) and increased Bnp mRNA.
• No significant systolic dysfunction or AVS was observed.
• Elevated cardiac mRNA for Nox2, Vcam1, Mmp12, and inflammatory markers, with reduced Sod2, indicated oxidative stress and inflammation.

Conclusions:

• A cholesterol-enriched diet effectively models LVDD in rabbits without AVS or systolic dysfunction.
• This model exhibits cardiac inflammation and oxidative stress.
• The developed rabbit model is suitable for testing LVDD therapeutic strategies.